Pub Date : 2024-11-20DOI: 10.1177/0271678X241300394
Gabriele M Gassner, Nikou L Damestani, Natalie S Wheeler, Jan A Kufer, Shrikanth M Yadav, Sarah F Mellen, Katherine N Maina, David H Salat, Meher R Juttukonda
White matter lesions (WMLs) are prevalent with aging, and higher WML burden has been observed in older adults with vascular diseases. While the physiology underlying the formation of WMLs is not known, various risk factors are associated with high WML burden. Here, we investigated the relationship between vascular risk factors and microvascular physiology (i.e., oxygen supply and oxygen extraction fraction [OEF]) and their association with WML burden. Forty-one typically aging adults (60-80 years) were classified into high or low vascular risk based on common modifiable vascular risk factors (hypertension, diabetes, hyperlipidemia, and overweight). These groups were subdivided into high or low WML burden. Differences in microvascular physiology (oxygen supply and OEF) were then compared between and within groups. Overall, OEF was significantly higher in the high vascular risk group compared to the low vascular risk group (p < 0.01). In the low vascular risk subgroup, OEF was uniquely lower in the individuals with high WML versus low WML burden (p = 0.02), despite no differences in oxygen supply between these subgroups (p = 0.87). The coupling of impaired OEF with the absence of compensatory physiology, such as elevated oxygen supply, may represent an important mechanism underlying WML burden in individuals with low vascular risk factors.
{"title":"Cerebral microvascular physiology associated with white matter lesion burden differs by level of vascular risk in typically aging older adults.","authors":"Gabriele M Gassner, Nikou L Damestani, Natalie S Wheeler, Jan A Kufer, Shrikanth M Yadav, Sarah F Mellen, Katherine N Maina, David H Salat, Meher R Juttukonda","doi":"10.1177/0271678X241300394","DOIUrl":"https://doi.org/10.1177/0271678X241300394","url":null,"abstract":"<p><p>White matter lesions (WMLs) are prevalent with aging, and higher WML burden has been observed in older adults with vascular diseases. While the physiology underlying the formation of WMLs is not known, various risk factors are associated with high WML burden. Here, we investigated the relationship between vascular risk factors and microvascular physiology (i.e., oxygen supply and oxygen extraction fraction [OEF]) and their association with WML burden. Forty-one typically aging adults (60-80 years) were classified into high or low vascular risk based on common modifiable vascular risk factors (hypertension, diabetes, hyperlipidemia, and overweight). These groups were subdivided into high or low WML burden. Differences in microvascular physiology (oxygen supply and OEF) were then compared between and within groups. Overall, OEF was significantly higher in the high vascular risk group compared to the low vascular risk group (p < 0.01). In the low vascular risk subgroup, OEF was uniquely lower in the individuals with high WML versus low WML burden (p = 0.02), despite no differences in oxygen supply between these subgroups (p = 0.87). The coupling of impaired OEF with the absence of compensatory physiology, such as elevated oxygen supply, may represent an important mechanism underlying WML burden in individuals with low vascular risk factors.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241300394"},"PeriodicalIF":4.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-17DOI: 10.1177/0271678X241301261
Mathijs Bj Dijsselhof, Jorina Holtrop, Sarah-Naomi James, Carole H Sudre, Kirsty Lu, Luigi Lorenzini, Lyduine E Collij, Catherine J Scott, Emily N Manning, David L Thomas, Marcus Richards, Alun D Hughes, David M Cash, Frederik Barkhof, Jonathan M Schott, Jan Petr, Henk Jmm Mutsaerts
While the associations of mid-life cardiovascular risk factors with late-life white matter lesions (WMH) and cognitive decline have been established, the role of cerebral haemodynamics is unclear. We investigated the relation of late-life (69-71 years) arterial spin labelling (ASL) MRI-derived cerebral blood flow (CBF) with life-course cardiovascular risk factors (36-71 years) and late-life white matter hyperintensity (WMH) load in 282 cognitively healthy participants (52.8% female). Late-life (69-71 years) high systolic (B = -0.15) and diastolic (B = -0.25) blood pressure, and mean arterial pressure (B = -0.25) were associated with low grey matter (GM) CBF (p < 0.03), and white matter CBF (B = -0.25; B = -0.15; B = -0.13, p < 0.03, respectively). The association between systolic blood pressure and GM CBF differed between sexes (male/female B = -0.15/0.02, p = 0.04). No associations were found with early- or mid-life cardiovascular risk factors. Furthermore, WMHs were associated with cerebral haemodynamics but not cardiovascular risk factors. These findings suggest that cerebral blood flow autoregulation is able to maintain stable global cerebral haemodynamics until later in life. Future studies are encouraged to investigate why cardiovascular risk factors have differential effects on haemodynamics and WMH, and their implications for cognitive decline.
{"title":"Associations of life-course cardiovascular risk factors with late-life cerebral haemodynamics.","authors":"Mathijs Bj Dijsselhof, Jorina Holtrop, Sarah-Naomi James, Carole H Sudre, Kirsty Lu, Luigi Lorenzini, Lyduine E Collij, Catherine J Scott, Emily N Manning, David L Thomas, Marcus Richards, Alun D Hughes, David M Cash, Frederik Barkhof, Jonathan M Schott, Jan Petr, Henk Jmm Mutsaerts","doi":"10.1177/0271678X241301261","DOIUrl":"10.1177/0271678X241301261","url":null,"abstract":"<p><p>While the associations of mid-life cardiovascular risk factors with late-life white matter lesions (WMH) and cognitive decline have been established, the role of cerebral haemodynamics is unclear. We investigated the relation of late-life (69-71 years) arterial spin labelling (ASL) MRI-derived cerebral blood flow (CBF) with life-course cardiovascular risk factors (36-71 years) and late-life white matter hyperintensity (WMH) load in 282 cognitively healthy participants (52.8% female). Late-life (69-71 years) high systolic (B = -0.15) and diastolic (B = -0.25) blood pressure, and mean arterial pressure (B = -0.25) were associated with low grey matter (GM) CBF (p < 0.03), and white matter CBF (B = -0.25; B = -0.15; B = -0.13, p < 0.03, respectively). The association between systolic blood pressure and GM CBF differed between sexes (male/female B = -0.15/0.02, p = 0.04). No associations were found with early- or mid-life cardiovascular risk factors. Furthermore, WMHs were associated with cerebral haemodynamics but not cardiovascular risk factors. These findings suggest that cerebral blood flow autoregulation is able to maintain stable global cerebral haemodynamics until later in life. Future studies are encouraged to investigate why cardiovascular risk factors have differential effects on haemodynamics and WMH, and their implications for cognitive decline.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241301261"},"PeriodicalIF":4.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the central nervous system (CNS), neuronal function and dysfunction are critically dependent on mitochondrial integrity and activity. In damaged or diseased brains, mitochondrial dysfunction reduces adenosine triphosphate (ATP) levels and impairs ATP-dependent neural firing and neurotransmitter dynamics. Restoring mitochondrial capacity to generate ATP may be fundamental in restoring neuronal function. Recent studies in animals and humans have demonstrated that endogenous mitochondria may be released into the extracellular environment and transported or exchanged between cells in the CNS. Under pathological conditions in the CNS, intercellular mitochondria transfer contributes to new classes of signaling and multifunctional cellular activities, thereby triggering deleterious effects or promoting beneficial responses. Therefore, to take full advantage of the beneficial effects of mitochondria, it may be useful to transplant healthy and viable mitochondria into damaged tissues. In this review, we describe recent findings on the mechanisms of mitochondria transfer and provide an overview of experimental methodologies, including tissue sourcing, mitochondrial isolation, storage, and modification, aimed at optimizing mitochondria transplantation therapy for CNS disorders. Additionally, we examine the clinical relevance and potential strategies for the therapeutic application of mitochondria transplantation.
在中枢神经系统(CNS)中,神经元的功能和功能障碍严重依赖于线粒体的完整性和活性。在受损或患病的大脑中,线粒体功能障碍会降低三磷酸腺苷(ATP)水平,并损害依赖 ATP 的神经发射和神经递质动态。恢复线粒体产生 ATP 的能力可能是恢复神经元功能的基础。最近对动物和人类的研究表明,内源性线粒体可释放到细胞外环境中,并在中枢神经系统的细胞间运输或交换。在中枢神经系统病理条件下,细胞间线粒体转运有助于产生新的信号和多功能细胞活动,从而引发有害影响或促进有益反应。因此,为了充分利用线粒体的有益作用,将健康、有活力的线粒体移植到受损组织中可能是有益的。在这篇综述中,我们介绍了线粒体转移机制的最新发现,并概述了旨在优化中枢神经系统疾病线粒体移植疗法的实验方法,包括组织来源、线粒体分离、储存和修饰。此外,我们还探讨了线粒体移植的临床意义和潜在的治疗应用策略。
{"title":"Molecular and cellular mechanisms of mitochondria transfer in models of central nervous system disease.","authors":"Takafumi Nakano, Keiichi Irie, Koichi Matsuo, Kenichi Mishima, Yoshihiko Nakamura","doi":"10.1177/0271678X241300223","DOIUrl":"10.1177/0271678X241300223","url":null,"abstract":"<p><p>In the central nervous system (CNS), neuronal function and dysfunction are critically dependent on mitochondrial integrity and activity. In damaged or diseased brains, mitochondrial dysfunction reduces adenosine triphosphate (ATP) levels and impairs ATP-dependent neural firing and neurotransmitter dynamics. Restoring mitochondrial capacity to generate ATP may be fundamental in restoring neuronal function. Recent studies in animals and humans have demonstrated that endogenous mitochondria may be released into the extracellular environment and transported or exchanged between cells in the CNS. Under pathological conditions in the CNS, intercellular mitochondria transfer contributes to new classes of signaling and multifunctional cellular activities, thereby triggering deleterious effects or promoting beneficial responses. Therefore, to take full advantage of the beneficial effects of mitochondria, it may be useful to transplant healthy and viable mitochondria into damaged tissues. In this review, we describe recent findings on the mechanisms of mitochondria transfer and provide an overview of experimental methodologies, including tissue sourcing, mitochondrial isolation, storage, and modification, aimed at optimizing mitochondria transplantation therapy for CNS disorders. Additionally, we examine the clinical relevance and potential strategies for the therapeutic application of mitochondria transplantation.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241300223"},"PeriodicalIF":4.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1177/0271678X241289756
Eszter Farkas, Christine R Rose
Brain pH is precisely regulated, and pH transients associated with activity are rapidly restored under physiological conditions. During ischemia, the brain's ability to buffer pH changes is rapidly depleted. Tissue oxygen deprivation causes a shift from aerobic to anaerobic metabolism and the accumulation of lactic acid and protons. Although the degree of tissue acidosis resulting from ischemia depends on the severity of the ischemia, spreading depolarization (SD) events emerge as central elements to determining ischemic tissue acidosis. A marked decrease in tissue pH during cerebral ischemia may exacerbate neuronal injury, which has become known as acidotoxicity, in analogy to excitotoxicity. The cellular pathways underlying acidotoxicity have recently been described in increasing detail. The molecular structure of acid or base carriers and acidosis-activated ion channels, the precise (dys)homeostatic conditions under which they are activated, and their possible role in severe ischemia have been addressed. The expanded understanding of acidotoxic mechanisms now provides an opportunity to reevaluate the contexts that lead to acidotoxic injury. Here, we review the specific cellular pathways of acidotoxicity and demonstrate that SD plays a central role in activating the molecular machinery leading to acid-induced damage. We propose that SD is a key contributor to acidotoxic injury in cerebral ischemia.
{"title":"A dangerous liaison: Spreading depolarization and tissue acidification in cerebral ischemia.","authors":"Eszter Farkas, Christine R Rose","doi":"10.1177/0271678X241289756","DOIUrl":"https://doi.org/10.1177/0271678X241289756","url":null,"abstract":"<p><p>Brain pH is precisely regulated, and pH transients associated with activity are rapidly restored under physiological conditions. During ischemia, the brain's ability to buffer pH changes is rapidly depleted. Tissue oxygen deprivation causes a shift from aerobic to anaerobic metabolism and the accumulation of lactic acid and protons. Although the degree of tissue acidosis resulting from ischemia depends on the severity of the ischemia, spreading depolarization (SD) events emerge as central elements to determining ischemic tissue acidosis. A marked decrease in tissue pH during cerebral ischemia may exacerbate neuronal injury, which has become known as acidotoxicity, in analogy to excitotoxicity. The cellular pathways underlying acidotoxicity have recently been described in increasing detail. The molecular structure of acid or base carriers and acidosis-activated ion channels, the precise (dys)homeostatic conditions under which they are activated, and their possible role in severe ischemia have been addressed. The expanded understanding of acidotoxic mechanisms now provides an opportunity to reevaluate the contexts that lead to acidotoxic injury. Here, we review the specific cellular pathways of acidotoxicity and demonstrate that SD plays a central role in activating the molecular machinery leading to acid-induced damage. We propose that SD is a key contributor to acidotoxic injury in cerebral ischemia.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241289756"},"PeriodicalIF":4.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1177/0271678X241298588
Kristina M Zvolanek, Jackson E Moore, Kelly Jarvis, Sarah J Moum, Molly G Bright
Cerebrovascular imaging assessments are particularly challenging in adolescent cohorts, where not all modalities are appropriate, and rapid brain maturation alters hemodynamics at both macro- and microvascular scales. In a preliminary sample of healthy adolescents (n = 12, 8-25 years), we investigated relationships between 4D flow MRI-derived blood velocity and blood flow in bilateral anterior, middle, and posterior cerebral arteries and BOLD cerebrovascular reactivity (CVR) in associated vascular territories. As hypothesized, higher velocities in large arteries are associated with an earlier response to a vasodilatory stimulus (cerebrovascular reactivity delay) in the downstream territory. Higher blood flow through these arteries is associated with a larger BOLD response to a vasodilatory stimulus (cerebrovascular reactivity amplitude) in the associated territory. These trends are consistent in a case study of adult moyamoya disease. In our small adolescent cohort, macrovascular-microvascular relationships for velocity/delay and flow/CVR change with age, though underlying mechanisms are unclear. Our work emphasizes the need to better characterize this key stage of human brain development, when cerebrovascular hemodynamics are changing, and standard imaging methods offer limited insight into these processes. We provide important normative data for future comparisons in pathology, where combining macro- and microvascular assessments may better help us prevent, stratify, and treat cerebrovascular disease.
{"title":"Macrovascular blood flow and microvascular cerebrovascular reactivity are regionally coupled in adolescence.","authors":"Kristina M Zvolanek, Jackson E Moore, Kelly Jarvis, Sarah J Moum, Molly G Bright","doi":"10.1177/0271678X241298588","DOIUrl":"10.1177/0271678X241298588","url":null,"abstract":"<p><p>Cerebrovascular imaging assessments are particularly challenging in adolescent cohorts, where not all modalities are appropriate, and rapid brain maturation alters hemodynamics at both macro- and microvascular scales. In a preliminary sample of healthy adolescents (n = 12, 8-25 years), we investigated relationships between 4D flow MRI-derived blood velocity and blood flow in bilateral anterior, middle, and posterior cerebral arteries and BOLD cerebrovascular reactivity (CVR) in associated vascular territories. As hypothesized, higher velocities in large arteries are associated with an earlier response to a vasodilatory stimulus (cerebrovascular reactivity delay) in the downstream territory. Higher blood flow through these arteries is associated with a larger BOLD response to a vasodilatory stimulus (cerebrovascular reactivity amplitude) in the associated territory. These trends are consistent in a case study of adult moyamoya disease. In our small adolescent cohort, macrovascular-microvascular relationships for velocity/delay and flow/CVR change with age, though underlying mechanisms are unclear. Our work emphasizes the need to better characterize this key stage of human brain development, when cerebrovascular hemodynamics are changing, and standard imaging methods offer limited insight into these processes. We provide important normative data for future comparisons in pathology, where combining macro- and microvascular assessments may better help us prevent, stratify, and treat cerebrovascular disease.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241298588"},"PeriodicalIF":4.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-09DOI: 10.1177/0271678X241299960
Allison Brookshier, Patrick Lyden
Currently, successful preclinical cerebroprotective agents fail to translate effectively into clinical practice suggesting the need for a comprehensive evaluation of all aspects of brain function. Selective vulnerability refers to the specific regional response of the brain following global ischemia, with observed patterns of vulnerability attributed to the distribution of neuronal subtypes and the functions of respective brain regions. Conversely, the concept of differential vulnerability pertains to the cell-type-specific reactions to cerebral ischemia, dictated by the biological characteristics of individual cells. This review aims to explore these vulnerability hypotheses and elucidate potential underlying cellular mechanisms.
{"title":"Differential vulnerability among cell types in the neurovascular unit: Description and mechanisms.","authors":"Allison Brookshier, Patrick Lyden","doi":"10.1177/0271678X241299960","DOIUrl":"10.1177/0271678X241299960","url":null,"abstract":"<p><p>Currently, successful preclinical cerebroprotective agents fail to translate effectively into clinical practice suggesting the need for a comprehensive evaluation of all aspects of brain function. Selective vulnerability refers to the specific regional response of the brain following global ischemia, with observed patterns of vulnerability attributed to the distribution of neuronal subtypes and the functions of respective brain regions. Conversely, the concept of differential vulnerability pertains to the cell-type-specific reactions to cerebral ischemia, dictated by the biological characteristics of individual cells. This review aims to explore these vulnerability hypotheses and elucidate potential underlying cellular mechanisms.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241299960"},"PeriodicalIF":4.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1177/0271678X241298584
Praveena Elanghovan, Thanh Nguyen, Pascal Spincemaille, Ajay Gupta, Yi Wang, Junghun Cho
The study investigated the sensitivity of a novel MRI-based OEF mapping, quantitative susceptibility mapping plus quantitative blood oxygen level-dependent imaging (QSM+qBOLD or QQ), to physiological changes, particularly increased oxygen extraction fraction (OEF) by using hyperventilation as a vasoconstrictive stimulus. While QQ's sensitivity to decreased OEF during hypercapnia has been demonstrated, its sensitivity to increased OEF levels, crucial for cerebrovascular disorders like vascular dementia and Parkinson's disease, remains unexplored. In comparison with a previous QSM-based OEF, we evaluated QQ's sensitivity to high OEF values. MRI data were obtained from 11 healthy subjects during resting state (RS) and hyperventilation state (HV) using a 3 T MRI with a three-dimensional multi-echo gradient echo sequence (mGRE) and arterial spin labeling (ASL). Region of interest (ROI) analysis and paired t-tests were used to compare OEF, CMRO2 and CBF between QQ and QSM. Similar to QSM, QQ showed higher OEF during HV compared to RS: in cortical gray matter, QQ-OEF and QSM-OEF was 36.44.7% and 35.312.5% at RS and 45.011.6% and 45.014.8% in HV, respectively. These findings demonstrate QQ's ability to detect physiological changes and suggest its potential in studying brain metabolism in neurological disorders.
{"title":"Sensitivity assessment of QSM+qBOLD (or QQ) in detecting elevated oxygen extraction fraction (OEF) in physiological change.","authors":"Praveena Elanghovan, Thanh Nguyen, Pascal Spincemaille, Ajay Gupta, Yi Wang, Junghun Cho","doi":"10.1177/0271678X241298584","DOIUrl":"https://doi.org/10.1177/0271678X241298584","url":null,"abstract":"<p><p>The study investigated the sensitivity of a novel MRI-based OEF mapping, quantitative susceptibility mapping plus quantitative blood oxygen level-dependent imaging (QSM+qBOLD or QQ), to physiological changes, particularly increased oxygen extraction fraction (OEF) by using hyperventilation as a vasoconstrictive stimulus. While QQ's sensitivity to decreased OEF during hypercapnia has been demonstrated, its sensitivity to increased OEF levels, crucial for cerebrovascular disorders like vascular dementia and Parkinson's disease, remains unexplored. In comparison with a previous QSM-based OEF, we evaluated QQ's sensitivity to high OEF values. MRI data were obtained from 11 healthy subjects during resting state (RS) and hyperventilation state (HV) using a 3 T MRI with a three-dimensional multi-echo gradient echo sequence (mGRE) and arterial spin labeling (ASL). Region of interest (ROI) analysis and paired t-tests were used to compare OEF, CMRO<sub>2</sub> and CBF between QQ and QSM. Similar to QSM, QQ showed higher OEF during HV compared to RS: in cortical gray matter, QQ-OEF and QSM-OEF was 36.4<math><mo> </mo><mo>±</mo><mo> </mo></math>4.7% and 35.3<math><mo> </mo><mo>±</mo><mo> </mo></math>12.5% at RS and 45.0<math><mo> </mo><mo>±</mo><mo> </mo></math>11.6% and 45.0<math><mo> </mo><mo>±</mo><mo> </mo></math>14.8% in HV, respectively. These findings demonstrate QQ's ability to detect physiological changes and suggest its potential in studying brain metabolism in neurological disorders.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241298584"},"PeriodicalIF":4.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1177/0271678X241296799
Takuma Nishimoto, Fumiaki Oka, Takao Inoue, Hiroshi Moriyama, Reo Kawano, Michiyasu Suzuki, David Y Chung, Cenk Ayata, Hideyuki Ishihara
Spreading depolarization (SD) develops after stroke and traumatic brain injury and may contribute to secondary brain damage. These diseases are often accompanied by intracranial hypertension, but little is known about the effects of intracranial pressure (ICP) on SD. Here, we study the effect of increased ICP on hemodynamic and metabolic response to SD in rats. SDs were triggered at different ICPs and cerebral perfusion pressures (CPP). The regional cerebral blood flow (rCBF), partial pressure of brain tissue oxygen (PbtO2), cerebral extracellular glucose and lactate concentrations were recorded. Fluoro-Jade staining was used to quantify neuronal injury in cortex. At high ICP (50 mmHg) with low CPP (30 mmHg), rCBF and PbtO2 were monophasically decreased in contrast to a monophasically increased pattern under normal conditions. Neuronal death increased in both hemispheres but much more on the side where SDs were triggered. At high ICP (50 mmHg) with normal CPP (70 mmHg), CBF and metabolism during SD did not differ from baseline, and neuronal death did not increase even on the side of SD induction. These data suggest that maintaining CPP at 70 mmHg, even when the ICP is as high as 50 mmHg, preserves normal blood flow and metabolism during SD events and prevents neuronal degeneration.
{"title":"Impact of intracranial hypertension and cerebral perfusion pressure on spreading depolarization.","authors":"Takuma Nishimoto, Fumiaki Oka, Takao Inoue, Hiroshi Moriyama, Reo Kawano, Michiyasu Suzuki, David Y Chung, Cenk Ayata, Hideyuki Ishihara","doi":"10.1177/0271678X241296799","DOIUrl":"10.1177/0271678X241296799","url":null,"abstract":"<p><p>Spreading depolarization (SD) develops after stroke and traumatic brain injury and may contribute to secondary brain damage. These diseases are often accompanied by intracranial hypertension, but little is known about the effects of intracranial pressure (ICP) on SD. Here, we study the effect of increased ICP on hemodynamic and metabolic response to SD in rats. SDs were triggered at different ICPs and cerebral perfusion pressures (CPP). The regional cerebral blood flow (rCBF), partial pressure of brain tissue oxygen (PbtO<sub>2</sub>), cerebral extracellular glucose and lactate concentrations were recorded. Fluoro-Jade staining was used to quantify neuronal injury in cortex. At high ICP (50 mmHg) with low CPP (30 mmHg), rCBF and PbtO2 were monophasically decreased in contrast to a monophasically increased pattern under normal conditions. Neuronal death increased in both hemispheres but much more on the side where SDs were triggered. At high ICP (50 mmHg) with normal CPP (70 mmHg), CBF and metabolism during SD did not differ from baseline, and neuronal death did not increase even on the side of SD induction. These data suggest that maintaining CPP at 70 mmHg, even when the ICP is as high as 50 mmHg, preserves normal blood flow and metabolism during SD events and prevents neuronal degeneration.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241296799"},"PeriodicalIF":5.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-02DOI: 10.1177/0271678X241291958
Ylenia Giarratano, Elizabeth A Hill, Charlene Hamid, Stewart Wiseman, Calum Gray, Francesca M Chappell, Roberto Duarte Coello, Maria C Valdés-Hernández, Lucia Ballerini, Michael S Stringer, Michael J Thrippleton, Daniela Jaime Garcia, Xiaodi Liu, William Hewins, Yajun Cheng, Sandra E Black, Andrew Lim, Rosa Sommer, Joel Ramirez, Bradley J MacIntosh, Rosalind Brown, Fergus Doubal, Tom MacGillivray, Joanna M Wardlaw, Renata Riha, Miguel O Bernabeu
Optical coherence tomography angiography (OCT-A) retinal imaging enables in vivo visualization of the retinal microvasculature that is developmentally related to the brain and can offer insight on cerebrovascular health. We investigated retinal phenotypes and neuroimaging markers of small vessel disease (SVD) in individuals with obstructive sleep apnoea (OSA). We enrolled 44 participants (mean age 50.1 ± SD 9.1 years) and performed OCT-A imaging before and after continuous positive airway pressure (CPAP) therapy. Pre-treatment analyses using a generalized estimating equations model adjusted for relevant covariates, revealed perivascular spaces (PVS) volume in basal ganglia associated with greater foveal vessel density (fVD) (p-value < 0.001), and smaller foveal avascular zone area (p-value = 0.01), whereas PVS count in centrum semiovale associated with lower retinal vessel radius (p-value = 0.02) and higher vessel tortuosity (p-value = 0.01). A reduction in retinal vessel radius was also observed with increased OSA severity (p-value = 0.05). Post-treatment analyses showed greater CPAP usage was associated with a decrease in fVD (p-value = 0.02), and increased retinal vessel radius (p-value = 0.01). The findings demonstrate for the first time the potential use of OCT-A to monitor CPAP treatment and its possible impact on both retinal and brain vascular health.
{"title":"Retinal microvascular phenotypes can track small vessel disease burden and CPAP treatment effectiveness in obstructive sleep apnoea.","authors":"Ylenia Giarratano, Elizabeth A Hill, Charlene Hamid, Stewart Wiseman, Calum Gray, Francesca M Chappell, Roberto Duarte Coello, Maria C Valdés-Hernández, Lucia Ballerini, Michael S Stringer, Michael J Thrippleton, Daniela Jaime Garcia, Xiaodi Liu, William Hewins, Yajun Cheng, Sandra E Black, Andrew Lim, Rosa Sommer, Joel Ramirez, Bradley J MacIntosh, Rosalind Brown, Fergus Doubal, Tom MacGillivray, Joanna M Wardlaw, Renata Riha, Miguel O Bernabeu","doi":"10.1177/0271678X241291958","DOIUrl":"10.1177/0271678X241291958","url":null,"abstract":"<p><p>Optical coherence tomography angiography (OCT-A) retinal imaging enables <i>in vivo</i> visualization of the retinal microvasculature that is developmentally related to the brain and can offer insight on cerebrovascular health. We investigated retinal phenotypes and neuroimaging markers of small vessel disease (SVD) in individuals with obstructive sleep apnoea (OSA). We enrolled 44 participants (mean age 50.1 ± SD 9.1 years) and performed OCT-A imaging before and after continuous positive airway pressure (CPAP) therapy. Pre-treatment analyses using a generalized estimating equations model adjusted for relevant covariates, revealed perivascular spaces (PVS) volume in basal ganglia associated with greater foveal vessel density (fVD) (p-value < 0.001), and smaller foveal avascular zone area (p-value = 0.01), whereas PVS count in centrum semiovale associated with lower retinal vessel radius (p-value = 0.02) and higher vessel tortuosity (p-value = 0.01). A reduction in retinal vessel radius was also observed with increased OSA severity (p-value = 0.05). Post-treatment analyses showed greater CPAP usage was associated with a decrease in fVD (p-value = 0.02), and increased retinal vessel radius (p-value = 0.01). The findings demonstrate for the first time the potential use of OCT-A to monitor CPAP treatment and its possible impact on both retinal and brain vascular health.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241291958"},"PeriodicalIF":5.4,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-06-17DOI: 10.1177/0271678X241261771
Ingeborg Rasing, Naomi Vlegels, Manon R Schipper, Sabine Voigt, Emma A Koemans, Kanishk Kaushik, Rosemarie van Dort, Thijs W van Harten, Alberto De Luca, Ellis S van Etten, Erik W van Zwet, Mark A van Buchem, Huub Am Middelkoop, Geert Jan Biessels, Gisela M Terwindt, Matthias Jp van Osch, Marianne Aa van Walderveen, Marieke Jh Wermer
Peak width of skeletonized mean diffusivity (PSMD) is an emerging diffusion-MRI based marker to study subtle early alterations to white matter microstructure. We assessed PSMD over the clinical continuum in Dutch-type hereditary CAA (D-CAA) and its association with other CAA-related MRI-markers and cognitive symptoms. We included (pre)symptomatic D-CAA mutation-carriers and calculated PSMD from diffusion-MRI data. Associations between PSMD-levels, cognitive performance and CAA-related MRI-markers were assessed with linear regression models. We included 59 participants (25/34 presymptomatic/symptomatic; mean age 39/58 y). PSMD-levels increased with disease severity and were higher in symptomatic D-CAA mutation-carriers (median [range] 4.90 [2.77-9.50]mm2/s × 10-4) compared with presymptomatic mutation-carriers (2.62 [1.96-3.43]mm2/s × 10-4) p = <0.001. PSMD was positively correlated with age, CAA-SVD burden on MRI (adj.B [confidence interval] = 0.42 [0.16-0.67], p = 0.002), with number of cerebral microbleeds (adj.B = 0.30 [0.08-0.53], p = 0.009), and with both deep (adj.B = 0.46 [0.22-0.69], p = <0.001) and periventricular (adj.B = 0.38 [0.13-0.62], p = 0.004) white matter hyperintensities. Increasing PSMD was associated with decreasing Trail Making Test (TMT)-A performance (B = -0.42 [-0.69-0.14], p = 0.04. In D-CAA mutation-carriers microstructural white matter damage is associated with disease phase, CAA burden on MRI and cognitive impairment as reflected by a decrease in information processing speed. PSMD, as a global measure of alterations to the white matter microstructure, may be a useful tool to monitor disease progression in CAA.
{"title":"Microstructural white matter damage on MRI is associated with disease severity in Dutch-type cerebral amyloid angiopathy.","authors":"Ingeborg Rasing, Naomi Vlegels, Manon R Schipper, Sabine Voigt, Emma A Koemans, Kanishk Kaushik, Rosemarie van Dort, Thijs W van Harten, Alberto De Luca, Ellis S van Etten, Erik W van Zwet, Mark A van Buchem, Huub Am Middelkoop, Geert Jan Biessels, Gisela M Terwindt, Matthias Jp van Osch, Marianne Aa van Walderveen, Marieke Jh Wermer","doi":"10.1177/0271678X241261771","DOIUrl":"10.1177/0271678X241261771","url":null,"abstract":"<p><p>Peak width of skeletonized mean diffusivity (PSMD) is an emerging diffusion-MRI based marker to study subtle early alterations to white matter microstructure. We assessed PSMD over the clinical continuum in Dutch-type hereditary CAA (D-CAA) and its association with other CAA-related MRI-markers and cognitive symptoms. We included (pre)symptomatic D-CAA mutation-carriers and calculated PSMD from diffusion-MRI data. Associations between PSMD-levels, cognitive performance and CAA-related MRI-markers were assessed with linear regression models. We included 59 participants (25/34 presymptomatic/symptomatic; mean age 39/58 y). PSMD-levels increased with disease severity and were higher in symptomatic D-CAA mutation-carriers (median [range] 4.90 [2.77-9.50]mm<sup>2</sup>/s × 10<sup>-4</sup>) compared with presymptomatic mutation-carriers (2.62 [1.96-3.43]mm<sup>2</sup>/s × 10<sup>-4</sup>) p = <0.001. PSMD was positively correlated with age, CAA-SVD burden on MRI (adj.B [confidence interval] = 0.42 [0.16-0.67], p = 0.002), with number of cerebral microbleeds (adj.B = 0.30 [0.08-0.53], p = 0.009), and with both deep (adj.B = 0.46 [0.22-0.69], p = <0.001) and periventricular (adj.B = 0.38 [0.13-0.62], p = 0.004) white matter hyperintensities. Increasing PSMD was associated with decreasing Trail Making Test (TMT)-A performance (B = -0.42 [-0.69-0.14], p = 0.04. In D-CAA mutation-carriers microstructural white matter damage is associated with disease phase, CAA burden on MRI and cognitive impairment as reflected by a decrease in information processing speed. PSMD, as a global measure of alterations to the white matter microstructure, may be a useful tool to monitor disease progression in CAA.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1253-1261"},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}